The initial event in the formation of urine is filtration of plasma across the glomerular capillary membrane. The normal glomerulus passes a filtrate containing a greatly decreased content of proteins with molecular masses greater than 45,000 daltons. Smaller plasma proteins are filtered through the glomerulus and then mostly reabsorbed by the proximal tubules, a small amount of protein is also derived from the urinary tract itself. The nett result is a urinary protein excretion of less than 150 mg/day. Renal diseases will affect the normal handling of proteins leading in many cases to an increased concentration of protein in the urine. Pathological proteinurias can be classified as glomerular, tubular or overflow. In rarer cases the proteins derived or secreted from the urinary tract may be increased (additive or nephrogenic proteinuria).
Glomerular proteinuria results from increased transcapillary passage of proteins and is characterised by the loss of plasma proteins equal to or greater than albumin. The quantitative assessment of glomerular function by the measurement of IgG/albumin clearance is no longer recommended.
In those instances where renal biopsy is contraindicated, IgG/albumin clearance ratios can give limited information. A selective proteinuria is consistent with steroid sensitive nephrosis. The exceptions to this general rule include pre-eclampsia where the selectivity ratio is typically between 0.20 and 0.40 yet the renal damage is fully reversible, and amyloidosis where the selectivity ratio is <0.16 and the renal condition progressive.
Tubular proteinuria results from a decrease in the capacity of the tubules to reabsorb protein and results in an increase in excretion of low molecular weight proteins, with electrophoretic mobilities mainly in the a 2- and b -region. The protein which is most suitable for the detection of tubular proteinuria is retinol-binding protein
b2microglobulin should no longer be considered a suitable marker for tubular proteinuria because of its pH instability.
Overflow proteinuria occurs when increased serum concentrations of proteins of low molecular mass are filtered through the glomerulus and exceed the reabsorptive capacity of tubules. Bence Jones proteinuria is the classic example, although excess haemoglobin and myoglobin are excreted in this way and give rise to urine which is red-brown in colour.
Bence Jones protein should be detected by electrophoresis of urine as passed, or after concentration, depending on the sensitivity of the protein stain used. The test of the adequate sensitivity of the method is that albumin should be visible in all urines studied. Following electrophoresis that demonstrates protein bands in addition to albumin, Bence Jones Protein should be confirmed or excluded by immunofixation.
Dipstick testing for urine protein will NOT detect Bence Jones Protein.
Sample requirement: 2 mL serum and 25 mL urine. The samples MUST be collected within the same four hour period.
IgG/albumin clearance ratios:
|0.16 – 0.30
Centres offering this assay:
London St George’s Hospital PRU Diagnostic Service
Sheffield Northern General’s PRU Diagnostic Service